Objective: Anxiety is one of the most common psychiatric symptoms of Parkinson’s disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit.Methods: Sixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed.Results: PD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p < 0.01; hippocampus: r = 0.496, p < 0.01).Conclusion: Our findings support the idea that anxiety in PD is associated with iron burden in the brain fear circuit, providing a possible new approach to explaining the potential neural mechanism of anxiety in PD.

Objective: White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective.Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system.Results: The 149 CSVD patients included 20 cases of “Type I mismatch,” 51 cases of Type I match, 38 cases of “Type II mismatch,” and 40 cases of “Type II match.” Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between “Type I match” and “Type I mismatch”; the FT of States 1 and 4 differed significantly between “Type II match” and “Type II mismatch.” Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between “Type I match” and “Type I mismatch,” while the left MTA score differed between “Type II match” and “Type II mismatch.”Conclusion: Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

Cerebral iron deposition is a pathological hallmark of Parkinson's disease. Notably, Parkinson's disease patients exhibit the characteristic neuroimaging features of enlarged choroid plexus volume (CPV) and diminished glymphatic function. While previous research has focused on potential iron influx dysregulation in Parkinson's disease, the critical question of whether impaired iron clearance stemming from choroid plexus and glymphatic system dysfunction constitutes a key mechanism underlying pathological iron accumulation remains unexplored. Therefore, the aim of this study was to investigate the relationship between cerebral iron deposition and glymphatic dysfunction in Parkinson's disease, and explored its clinical relevance. We hypothesized that impaired glymphatic clearance contributes to pathological iron accumulation in Parkinson's disease. This cross-sectional study enrolled 65 patients with mild-to-moderate Parkinson's disease and 38 age- and sex-matched healthy controls. Multimodal MRI was used to assess the CPV, diffusion tensor imaging analysis along the perivascular space (ALPS) index (indirectly reflecting glymphatic function) and quantitative susceptibility mapping-derived iron levels. The clinical evaluations included motor, cognitive and psychiatric assessments. Statistical analyses compared group differences, correlations, mediation effects and diagnostic performance via receiver operating characteristic analysis. Compared to healthy controls, Parkinson's disease patients exhibited bilateral CPV enlargement (P < 0.01), reduced ALPS indices (P < 0.05) and elevated iron deposition in the substantia nigra, red nucleus and putamen (P < 0.05). CPV negatively correlated with ALPS index (left hemisphere: r = −0.305, P = 0.014; right hemisphere: r = −0.357, P = 0.004). Notably, the degree of glymphatic dysfunction, manifested by either choroid plexus enlargement or a reduced ALPS index, was significantly correlated with regional iron deposition patterns, especially between the CPV and substantia nigra iron deposition (left hemisphere: r = 0.236, P = 0.029; right hemisphere: r = 0.233, P = 0.031). Mediation analysis revealed that ALPS and putamen iron deposition-mediated CPV affected daily living impairments and psychiatric symptoms. A comprehensive diagnostic model integrating neuroimaging, cognitive and psychiatric variables achieved near-perfect discrimination for mild-to-moderate Parkinson's disease (area under the receiver operating characteristic curve = 0.972, sensitivity = 100%, specificity = 97.4%). In conclusion, our results suggest that CPV enlargement and reduced ALPS index are closely linked to pathological iron deposition in Parkinson's disease. These biomarkers correlate with motor deficits, cognitive decline and psychiatric symptoms, highlighting their roles in disease progression. The integrated diagnostic model demonstrated exceptional accuracy, advocating multimodal approaches for Parkinson's disease management. These findings suggest that glymphatic modulation and iron chelation are potential therapeutic targets that warrant further longitudinal validation.

Aims: This study aimed to explore the relationship between glymphatic dysfunction and anxiety in patients with Parkinson's disease (PD). Methods: A total of 21 patients with PD with anxiety (PD‐A), 47 patients with PD without anxiety (PD‐NA), and 38 healthy subjects were prospectively enrolled. Participants underwent neuropsychiatric assessment, motor examinations, and magnetic resonance imaging. Brain glymphatic function was evaluated using diffusion tensor image analysis along the perivascular spaces (DTI‐ALPS) and global blood oxygen level‐dependent signal and cerebrospinal fluid dynamics coupling (gBOLD‐CSF coupling). Correlations between glymphatic function and anxiety (quantified using Hamilton Anxiety Rating Scale [HAMA] scores) were analyzed. Receiver operating characteristic analysis was used to assess the diagnostic performance of clinical features, ALPS index, and gBOLD‐CSF coupling strength, and multivariate models were used to distinguish patients with PD‐A from those with PD‐NA. Results: The PD‐A group exhibited longer PD duration, higher Hoehn and Yahr (H&Y) stage, and higher HAMA scores compared to the PD‐NA group. Both DTI‐ALPS and gBOLD‐CSF coupling analyses revealed significant glymphatic dysfunction in patients with PD‐A. The ALPS index and gBOLD‐CSF coupling strength were inversely correlated with HAMA scores and positively correlated with each other. The multivariate diagnostic model combining clinical variables and glymphatic indices outperformed univariate models. Conclusions: The DTI‐ALPS index and gBOLD‐CSF coupling strength may serve as novel neuroimaging markers for PD‐A, with diagnostic performance enhanced by combining these markers with clinical features.